Authors:Louloudis G.Abstract: Pain is a distressing physical and emotional experience associated with actual or potential tissue injury, or an experience described in terms of such injury. The primary function of nociceptors, such as some dorsal root ganglion (DRG) neurons, is to transduce noxious sensory modalities, e.g. mechanical pressure, cold and heat, into electrical impulses and to transmit these to processing centres in the central nervous system (CNS). Modality-specific pain pathways have been identified through in vivo deletion of voltage-gated Na+ channels in mouse DRG neurons. Deletion of Nav1.8 channels has been shown to result in loss of mechanosensory and cold-induced pain, but not-heat induced pain, whereas deletion of Nav1.7 channels has been seen to abolish responses to noxious heat and mechanical stimuli. The present review constitutes an attempt to elucidate the mechanisms through which voltage-gated Na+ channels are involved in modality-specific pain pathways. It has been found that Nav1.8 and Nav1.9 channels are resistant to slow inactivation upon cooling, maintaining activity even though channels on other sensory afferents may be inactivated. Nav1.7 channel activity is reported to be coupled to substance P release into the dorsal horn of dorsal root ganglion (DRG) neurons in heat-specific pain pathways. Recent research has also offered insight into the role of Nav1.7 and Nav1.9 mutations in pain-related conditions, e.g. inherited erythromelalgia and cold-aggravated pain, respectively, as these influence kinetic parameters, such as open state probability. Therefore, voltage-gated Na+ channels appear to be playing an important role in segregating modality-specific pain pathways. The identification of markers for mechanisms implicated in the activation of these pathways could potentially pave the way towards the development of more effective analgesics.PubDate: 2017-11-02DOI: 10.1093/biohorizons/hzx013Issue No:Vol. 10 (2017)

Authors:Townson J.Abstract: The development of programmable nucleases in the past two decades has enabled scientists to generate specific mutations to the genomes of many different organisms and tissues. Programmable nucleases including meganucleases, zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs) and RNA-guided engineered nucleases (RGENs), create double-stranded breaks in specific DNA sequences. Mutations can be introduced at these breaks during repair by non-homologous end joining (NHEJ) or homologous recombination (HR), this is gene editing. Application of gene editing in plants has been highly successful using programmable nucleases, with one of the main inhibitors of progress being the efficiency with which they can be transformed into plants. The more recently described RGENs were developed from clustered regularly interspaced palindromic repeat (CRISPR) sequences and CRISPR-associated (Cas) protein systems in bacteria. They provide a simple, adaptable and facile mechanism for gene editing, especially multiplex genome editing. Off-target effects are a cause for concern but the fast pace of research is quickly improving specificity and further developing CRISPR/Cas technology for other functions such as regulating gene transcription. The use of gene editing in crop plants could provide a solution towards establishing sustainable agriculture to support the worlds growing population and adapt to climate changes. Here the application of programmable nucleases in plants is reviewed and the potential future uses of CRISPR/Cas systems in plants discussed. The importance of establishing suitable regulatory procedures to deal with potentially transgene-free gene editing crops is also highlighted.PubDate: 2017-10-31DOI: 10.1093/biohorizons/hzx016Issue No:Vol. 10 (2017)

Authors:Ng’ong’a F; Nyanjom S, Adunga V, et al.Abstract: Trypanosomes are protozoans causing African trypanosomiasis, a neglected tropical disease in Africa affecting humans and animals. Control methods have focused on the use of drugs which have adverse effects and vector control methods which have proved to be ecologically unsustainable. However, no conventional vaccine exists due to antigenic variation. In trypanosomes, peptidases are widely implicated as virulence factors thus could be targeted in the development in new therapeutic agents. This study predicts the presence of three putative tricorn protease interacting factor 3 genes in Trypanosoma brucei brucei, two of which appear to represent gene duplication. The genes were identified through a combination of PSI-BLAST, orthology clustering and structure predictions. Motif conservation was predicted through MEME suite and STRING database was used to predict protein–protein interactions. Both sequence and structural prediction showed considerable conservation among the homologues. The overall predicted structures of the putative Trf 3 homologues in T. b. brucei had four domains; N-terminal domain I predominantly composed of β-sheets, catalytic domain II composed of mixed α/β structure, saddle-like domain III composed of β-sheets and C-terminal domain IV composed of α-helices, organized into a super helix. The active site with the zinc-binding motif ({HEXXH (18X) E}), the GXMEN motif specific for M1 family as well as the N-terminal substrate anchoring, glutamate and the proton acceptor, tyrosine were conserved. The STRING network predicted interaction between the putative Trf 3 homologues with proteasomal core complex through polyubiquitin suggesting that they could be proteasomal components.PubDate: 2017-10-19DOI: 10.1093/biohorizons/hzx012Issue No:Vol. 10 (2017)

Authors:Shorter E.Abstract: The analysis of human genomes has revealed an unexpectedly large variability among individuals of a population. This variation occurs via numerous different mechanisms and on many different scales, ranging from single nucleotide changes to the loss or gain of lengths of DNA encompassing entire genes. Research has often found associations between DNA sequence variations, such as single-nucleotide polymorphisms, and common human diseases (Shastry, 2002). However, research into the relationship between copy number variations (CNVs) and disease is relatively novel, with progress only being made in recent years. Here, I review literature on the relationship between CNV and obesity including the advances and challenges involved in such research.PubDate: 2017-10-19DOI: 10.1093/biohorizons/hzx014Issue No:Vol. 10 (2017)

Authors:Kansu BB; Lang DD.Abstract: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. A significant risk factor for developing CVD is the presence of high plasma levels of low-density lipoprotein (LDL) cholesterol. With regard to pharmacological intervention, ‘fat busting’ statins are seen as the wonder drugs for lipid lowering and reducing the risk of myocardial infraction and stroke. However, there is wide inter-patient variability in measureable responses to these HMG-CoA reductase inhibitors, with individual patient genotypes being increasingly recognized as important contributors to this phenomenon. In recent years there have been great advances in our understanding of how personal genetics plays a role in controlling responses to drug therapies. Nevertheless, to date, there is no clinical application of identifying genetic markers that may predict responses to statins and subsequently modify cardiovascular outcomes. This review discusses the current literature regarding the potential roles of individual genetic polymorphisms in influencing responses to statins, and whether this can translate into clinical benefits for patients. While the significance of individual single nucleotide polymorphisms is yet to be established, it is suggested from genome-wide association studies that combinations of polymorphisms could be of greater clinical relevance. Further studies investigating the long-term influence of personal genetics on responses to statins and hard clinical outcomes are essential. As technology advances and the cost of genome sequencing falls, it will become increasingly easier to use individual genetic profiles to predict drug responses, tailor treatments and provide clinical benefit across populations.PubDate: 2017-09-12DOI: 10.1093/biohorizons/hzx010Issue No:Vol. 10 (2017)

Authors:Williams HM.Abstract: Magnetic nanoparticles (MNPs) have shown promise in a number of biomedical applications, including: magnetic hyperthermia, enhancing magnetic resonance imaging (MRI) data, supplementing tissue engineering efforts and improving the delivery of drugs to difficult to reach microniches. Their inclusion in the treatment pathways of various pathologies highlights a growing trend towards the integration of novel biotechnologies in healthcare and therapeutic settings. Superparamagnetic nanoparticles (SPNs) allow clinicians to produce a localized thermo-ablative effect leading to the destruction of bacterial biofilms and cancer cells. In addition, through the physical disruption of bacterial membranes, SPNs can sensitize resistant bacterial cells to antibacterial compounds. MNPs have also improved the delivery of bactericidal compounds to restricted microniches, and could, therefore, potentially be used in the treatment of conditions that require therapeutic interventions to cross the blood–brain barrier. Furthermore, MNPs have been investigated as novel MRI contrast agents due to their unique combination of favourable magnetic properties, biodegradability, and surface functionality.PubDate: 2017-08-09DOI: 10.1093/biohorizons/hzx009Issue No:Vol. 10 (2017)

Authors:Wickham G.Abstract: Benzalkonium chloride is a common quaternary ammonium cation-based disinfectant used as an industrial-grade biocide, but little independent work has been undertaken quantifying the concentrations required for sterilization. This study investigated relative differences in resistance between common Gram-negative and Gram-positive bacterial pathogens and determined the complete sterilization concentrations for each. A membrane filtration methodology was used to quantify an enriched isolate of deionized water, which was subjected to various concentrations of disinfectant incubated on MacConkey agar. The colony forming units at each concentration were compared to an untreated control. Three main trends, defined as ‘phases of inhibition’, were observed across all isolates studied. Phase I occurred from 0 to 1 mL disinfectant/L water and displayed a moderate, consistent rate of inhibition. Phase II occurred from 0.1% to 0.4% biocide in solution and was characterized by a dramatic increase in inhibition and a divergence of inhibition rates for each organism. Phase III occurred from 0.4% biocide in solution onward and was characterized by the gradual decline in rate of inhibition until each organism reached total inhibition. It was found that the Gram-negative group, comprising Escherichia coli and Pseudomonas aeruginosa, was generally more resistant than the Gram-positive group, comprising Enterococcus faecalis and Staphylococcus aureus, p < 0.001, with the individual Gram-negative organisms, having the highest complete sterilization concentrations. It was also observed that a variation in resistance existed between organisms of the same Gram stain group. This resulted in some organisms exhibiting resistances comparable to that of organisms of the opposite group, namely between the E. faecalis and P. aeruginosa, which exhibited no significance difference, p = 0.080. Therefore, a model is proposed in which the Gram stain groups can be generalized as being distinct in terms of intrinsic resistance, but also that the range of resistance exists as a spectrum within each group which can cause a similarity between individual organisms of different groups.PubDate: 2017-07-28DOI: 10.1093/biohorizons/hzx008Issue No:Vol. 10 (2017)

Authors:Osborne A.Abstract: This review aims to highlight the key areas in which changes to the epigenome have played an important role in the evolution and development of our species. Firstly, there will be a brief introduction into the topic of epigenetics to outline the current understanding of the subject and inform the reader of the basic mechanisms and functions of the epigenome. This will lead on to more focussed detail on the role played by epigenetic changes in the rapid evolution of our species and emergence from our ancestor species, as well as the Human Accelerated Regions that played a role in this. The discussion highlights how epigenetics has helped and hindered our species’ development via changes to the epigenome in more modern times, discussing case examples of documented instances where it is shown that epigenetics has played a role in the evolution of humanity.PubDate: 2017-07-28DOI: 10.1093/biohorizons/hzx007Issue No:Vol. 10 (2017)

Authors:Fredrickson JO.Abstract: Traditionally, the genes which contribute to the phenotype of a eukaryotic organism were considered to be housed within its nuclear genome, but today this is often understood to not be the case. In order to better understand how high-level complex phenotypic expressions arise I propose a conceptual framework composed of core systems biology ideas integrated with current understanding of genetic systems: gene systems hypothesis (GSH). The implications of this GSH framework allow for an organism level functional gene system (O-FGS) definition which incorporates the integration of macro- and micro-symbiont gene systems. In support of the proposed O-FGS definition a brief review of current literature is presented which demonstrates the influence of micro- and macro-symbionts in plant and animal development, growth and persistence.PubDate: 2017-06-13DOI: 10.1093/biohorizons/hzx005Issue No:Vol. 10 (2017)

Authors:Ellis L.Abstract: Musicogenic epilepsy is a rare form of reflex epilepsy in which seizures are triggered by certain pieces of music. Musical processing involves interpretation of perceptual elements such as tempo and pitch, and also emotional associations and memory formation. It is hypothesized that the emotional impact of music is more likely to precipitate musicogenic seizures through involvement of the mesolimbic system. This may link these seizures to other types of reflex seizures that also involve emotional responses. Current treatment is restricted to anti-epileptic drugs and surgery, which is not always an option for patients due to eligibility or availability, for example in developing countries. The scientific literature on this topic is very limited. Individual case studies have stated that patients report techniques they use to stop seizures such as distraction, but these have not been explored. Online forums seem to suggest the condition is more common than the scientific literature states, and so may be a useful resource to consider. After describing the normal processing of music and how this pathway may be affected in musicogenic epilepsy, the review discusses the potential relationship between musicogenic and other seizures, and why this is relevant. New avenues for research into alternative interventions for patients could be opened by considering information on forums and case reports, and methods of doing this are discussed.PubDate: 2017-03-28DOI: 10.1093/biohorizons/hzx004Issue No:Vol. 10 (2017)

Authors:Jia Jiet L; Soma R. M.Abstract: The diet of young university adults in Malaysia is mainly dependent on the food providers in and around the campus. Limited Malaysian studies have employed 24-h urinary sodium to estimate dietary salt intake in young adults. The fifth National Health and Morbidity Survey (NHMS), Malaysia (2015) concluded that 30.3% of Malaysian adults aged 18 years and above have hypertension. The objective of this study was to investigate the dietary salt intake and blood pressure of young university adults and the relationship between these two variables. This study also estimated the macronutrient content of the foods frequently consumed by the study participants to explore the relationship between the macronutrients, salt and blood pressure. Twenty-eight participants aged between 18 and 25 years old were recruited. Blood pressure was measured using a digital blood pressure monitor. Anthropometric measurements of participants were taken using standard procedures. Twenty-four-hour urinary sodium was analysed using atomic absorption spectrophotometry (AAS). Food intake of the participants was surveyed by an interviewer-administered questionnaire to identify the sources of dietary salt. The mean salt intake of the participants was 10.80 ± 0.78 g/day (ranging from 5.71 g/day to 20.02 g/day), exceeding the recommendation of 5 g/day set by the National Coordinating Committee on Food and Nutrition Malaysia by 116%. The mean systolic blood pressure (SBP) was 104.43 ± 1.68 mmHg, and the mean diastolic blood pressure (DBP) was 66.46 ± 1.23 mmHg. A positive correlation was found between salt intake and SBP, though it was not statistically significant (r = 0.21, p = 0.30). Salt intake was significantly associated with body weight (r = 0.47, p = 0.01), body mass index (BMI) (r = 0.45, p = 0.02) and fat free mass (r = 0.44, p = 0.02); SBP was also significantly correlated with body weight (r = 0.61, p = 0.00), BMI (r = 0.54, p = 0.00) and fat free mass (r = 0.56, p = 0.00). The sodium content of the food products was significantly correlated with energy-adjusted protein content of the food (r = 0.67, p = 0.00). Individuals who consumed more than 10 g/day of salt were frequent consumers of ‘dried anchovies/cuttlefish/prawns’, ‘instant meals’, ‘fried rice/noodles’, ‘noodles with soup’ and ‘noodles with soy sauce’. Educating the local food providers to modify their recipes with reduced salt could be part of an integrated strategy to reduce salt intake among the population.PubDate: 2017-03-22DOI: 10.1093/biohorizons/hzx003Issue No:Vol. 10 (2017)

Authors:Bramham L; Pyke K.Abstract: Whilst plastids are fundamental to many aspects of plant biology and the production of enhanced crop cultivars, research into the dynamics of non-green plastids has remained somewhat disregarded by the scientific community compared to chloroplasts. They are equally pivotal to normal plant development however, and are now increasingly becoming the focus of research made possible by genetic manipulation and reporter gene constructs.The total plastid content of all plant cells originates from small, undifferentiated plastids termed proplastids found within the meristematic regions of both root and shoot tissue. The cellular regulatory mechanisms controlling the development of plastids in young tissues are poorly understood, especially in the case of non-green plastids in roots. This investigation consequently aimed to elucidate the differences in plastid content, morphology and subcellular localization within epidermal cells derived from the root and shoot apical meristems (RAM and SAM respectively) of Arabidopsis thaliana.Quantification of non-green plastids was facilitated via the use of confocal laser scanning microscopy in conjunction with the expression of plastid-targeted green fluorescent protein driven by a constitutive promoter. Characterization of early seedling development and tissue diversification was also achieved by assessing epidermal cell size relative to developmental progression, ultimately facilitating comparative analyses of plastid dynamics on both a temporal and tissue-varietal basis.The number of plastids in epidermal cells within RAM-derived tissue was shown to increase across regions of cell division before being regulated throughout subsequent zones of elongation and maturing root tissue. In contrast, epidermal cells of the hypocotyl exhibit a more generalized increase in plastid number and less strict maintenance of cell plan area coverage during tissue expansion.The findings presented here suggest the functioning of distinct mechanisms regulating plastid division and growth in relation to cell size within shoot and root apical meristem-derived tissues.PubDate: 2017-02-18DOI: 10.1093/biohorizons/hzx001Issue No:Vol. 10 (2017)

Authors:Ware FL; Luck MR.Abstract: Haemostasis is the prevention of blood fluidity in vertebrates and is the first stage of wound healing. Haematophagous animals use the blood of vertebrates as their sole source of nutrition and have evolved many salivary constituents to counteract the haemostatic response of their prey. These animals and their saliva have been studied for many years, with some applications in medicine. The purpose of this study is to compare the salivary constituents of leeches (Hirudinae), ticks (Argasidae and Ixodidae) and vampire bats (Desmodontinae) and to consider their evolutionary origin. Salivary constituents include plasminogen activators (PAs), anticoagulants (activated factor X, FXa; inhibitors), vasodilators, platelet aggregation inhibitors (PAgI) and thrombin inhibitors. The animals studied all tend to possess an anticoagulant and a form of apyrase (PAgI) to assist with blood feeding. Ticks and vampire bats have a form of PA but the leech does not. The vampire bat has a PAgI but no vasodilator. The animals studied are from taxonomically unrelated groups but exploit similar mechanisms of action to facilitate their haematophagy. Given that the haematophagous lifestyle of these animals developed much later than their common ancestors, we conclude that their mechanisms for haematophagy have arisen by convergent evolution. Some molecules, e.g. serine proteases found in invertebrate saliva, are probably derived from a common ancestral gene. The possible paths that have led to evolution of vampire bat salivary components are considered. Further research into the homology of these salivary constituents is required to give insight into how these animals adapted to haematophagy and their further therapeutic potential.PubDate: 2017-02-14DOI: 10.1093/biohorizons/hzw015Issue No:Vol. 10 (2017)

Authors:Jowett P; Rayne R, Tomas S.Abstract: Research into the origins of the first protocell is of a multidisciplinary nature. It draws evidence from what we know about the Earth’s early atmosphere and environment, and about the most ancient features of the cell’s structure and composition. Such data provides the input for the hypothesis generation and experimental reconstruction necessary to mimic steps in the formation of the first protocell. While research into the origins of the first protocell is condemned to focus upon laboratory experiments, it should be guided by a detailed study of real evidence pertaining to the environment on Earth 4 billion years ago. In this review, we take stock of the research that has been performed to date across the main disciplines of earth sciences, biochemistry, and molecular biology. We seek to identify the progress made in laying down a sequence for the events that led up to the first protocell. We also assess the strengths and weaknesses of the experimental designs and suggest some future approaches. While the field has made many important advances, from the original Stanley Miller experiment establishing ‘life from chemistry’ products such as amino acids, through to Deamer’s findings on fatty acid membranes and Szostack’s work on lipids, there is still a long and challenging journey ahead to understand how cellular life began. The experiments required to make more rapid progress in the field will likely be more elaborate, costly, and time consuming.PubDate: Tue, 05 Dec 2017 00:00:00 GMT

Authors:Smyth M. Abstract: Exact aetiology of most autoimmune diseases is unknown. Genetic predisposition, environmental factors, microbiota dysbiosis and the gut–brain axis are known to interplay in autoimmune disease development. Arresting such interplay, by implementing a particular diet (such as the low FODMAP diet) or by consuming specific drugs (such as zonulin antagonists) for example, will reduce disease symptoms, reverse intestinal hyperpermeability and allow remission. The aim of this study was to investigate possible mechanisms of autoimmune disease aetiology and alterations in intestinal permeability, specifically in coeliac disease and type 1 diabetes mellitus. This was done by collecting researched evidence from journals and other publications. Understanding the pathology of the diseases and identifying the particular genes and triggers involved as well as improving investigative methods will potentiate the development of prevention and treatment therapies.Methods: Collection of researched evidence was conducted from journals and other publications.PubDate: 2017-11-28

Authors:Stewart A. Abstract: Cases of lung cancer are increasing every year globally, with little improvement in survival rates. Therefore, the quality of life (QOL) of these patients is of increasing interest. This could mean that whilst undergoing treatment the impact on them both physically and mentally can be reduced from the stress of invasive and strong treatments. By looking at plants used medicinally in Traditional Chinese herbal Medicine (TCM), it is hoped that a source of QOL improvement can be found for patients. To investigate whether TCM could provide a source of new medicines that could improve QOL, a systematic literature search and meta-analysis was undertaken for randomized control trials published in this area. The quality and reliability of papers was also assessed to determine why further research has not yet been completed. This used a random effects model to take into account methodological differences when completing quantitative analysis. Heterogeneity analysis and publication bias of the included papers was also completed. A total of 1270 papers were initially screened with 10 being used in final analysis after applying exclusion and inclusion criteria. It was found that there was a small to medium summary Cohens D value of 0.33 (95% CI, −0.12, 0.78). However, the quality of these papers was found to be very poor leading to questions about their reliability and accuracy. There was also found to be a publication bias with only studies with statistically significant effects being published. In conclusion papers were poor quality and heterogeneity was high (I2 = 90.38%). Thus, making it difficult to determine if traditional Chinese herbal medicine has a beneficial effect on the quality of life of lung cancer patients and showing why research in this area has not been taken up more rapidly despite initial beneficial effects being found and discussed in research papers.PubDate: 2017-11-14